A whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer: a prospective study

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• 作者：Robert W Ross ; MD^a ; ^b ; ^&dagger ; ; Matthew D Galsky ; MD^c ; ^&dagger ; ; Prof Howard I Scher ; MD^d ; ^e ; Jay Magidson ; PhD^f ; Karl Wassmann ; MBA^g ; Gwo-Shu Mary Lee ; PhD^a ; ^b ; Leah Katz ; MD^a ; ^b ; Sumit K Subudhi ; MD^d ; ^e ; Aseem Anand ; MD^d ; ^e ; Martin Fleisher ; PhD^h ; Prof Philip W Kantoff ; MD^a ; ^b ; Prof William K Oh ; MD^c ; ^{william.oh@mssm.edu}
• 刊名：Lancet Oncology
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：13
• 期：11
• 页码：1105-1113
• 全文大小：423 K

文摘

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Summary

Background

Survival for patients with castration-resistant prostate cancer is highly variable. We assessed the effectiveness of a whole-blood RNA transcript-based model as a prognostic biomarker in castration-resistant prostate cancer.

Methods

Peripheral blood was prospectively collected from 62 men with castration-resistant prostate cancer on various treatment regimens who were enrolled in a training set at the Dana-Farber Cancer Institute (Boston, MA, USA) from August, 2006, to June, 2008, and from 140 patients with castration-resistant prostate cancer in a validation set from Memorial Sloan-Kettering Cancer Center (New York, NY, USA) from August, 2006, to February, 2009. A panel of 168 inflammation-related and prostate cancer-related genes was assessed with optimised quantitative PCR to assess biomarkers predictive of survival.

Findings

A six-gene model (consisting of ABL2, SEMA4D, ITGAL, and C1QA, TIMP1, CDKN1A) separated patients with castration-resistant prostate cancer into two risk groups: a low-risk group with a median survival of more than 34¡¤9 months (median survival was not reached) and a high-risk group with a median survival of 7¡¤8 months (95 % CI 1¡¤8-13¡¤9; p<0¡¤0001). The prognostic utility of the six-gene model was validated in an independent cohort. This model was associated with a significantly higher area under the curve compared with a clinicopathological model (0¡¤90 [95 % CI 0¡¤78-0¡¤96] vs 0¡¤65 [0¡¤52-0¡¤78]; p=0¡¤0067).

Interpretation

Transcriptional profiling of whole blood yields crucial prognostic information about men with castration-resistant prostate cancer. The six-gene model suggests possible dysregulation of the immune system, a finding that warrants further study.

Funding

Source MDX.